Hydroalcoholic Extract of Centella asiatica and Madecassic Acid Reverse Depressive-Like Behaviors, Inflammation and Oxidative Stress in Adult Rats Submitted to Stress in Early Life.

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Rats (after the first day of birth) were separated from the mother for 3 h a day for 10 days. When adults, these animals were divided into groups and submitted to treatment for 14 days. After subjecting the animals to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, researchers then euthanized the animals. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through anti-inflammatory and antioxidant profiles.

Dementia and depression: Biological connections with amyloid ß protein.

Dementia is an umbrella term for a broad group of age-associated neurodegenerative diseases. It is estimated that dementia affects 50 million people worldwide and that Alzheimer's disease (AD) is responsible for up to 75% of cases. Small extracellular senile plaques composed of filamentous aggregates of amyloid ß (Aß) protein tend to bind to neuronal receptors, affecting cholinergic, serotonergic, dopaminergic and noradrenergic neurotransmission, leading to neuroinflammation, among other pathophysiologic processes and subsequent neuronal death, followed by dementia. The amyloid cascade hypothesis points to a pathological process in the cleavage of the amyloid precursor protein (APP), resulting in pathological Aß. There is a close relationship between the pathologies that lead to dementia and depression. It is estimated that depression is prevalent in up to 90% of individuals diagnosed with Parkinson's disease, with varying severity, and in 20 to 30% of cases of Alzheimer's disease. The hypothalamic pituitary adrenal (HPA) axis is the great intermediary between the pathophysiological mechanisms in neurodegenerative diseases and depression. This review discusses the role of Aß protein in the pathophysiological mechanisms of dementia and depression, considering the HPA axis, neuroinflammation, oxidative stress, signalling pathways and neurotransmission.

Early Life Stress and Major Depressive Disorder-An Update on Molecular Mechanisms and Synaptic Impairments.

Early life stress (ELS), characterized as abuse, neglect, and abandonment, can cause several adverse consequences in the lives of affected individuals. ELS experiences can affect an individual's development in variable ways, persisting in the long term and promoting lasting impacts, considering that early exposure to stressors can be biologically incorporated, as prolonged stimulation of stress response systems affects the development of the brain structure and other body systems, increasing the risk of diseases associated with stress and cognitive impairment. This type of stress increases the risk of developing major depressive disorder (MDD) in a severe form that does not respond adequately to traditional antidepressant treatments. Several alterations are studied as mechanisms that relate ELS with MDD, such as epigenetic alterations, neurotransmitters, and neuronal signaling. This review discusses research that brings evidence about the ELS mechanisms involved in synaptic impairments and MDD. The processes involved in epigenetic changes and the HPA axis are highlighted, as well as changes in neurotransmitters and neuronal signaling mechanisms.

The Impact of Stress from Social Isolation during the COVID-19 Pandemic on Psychiatric Disorders: An Analysis from the Scientific Literature.

The COVID-19 pandemic generated, in addition to severe symptoms, hospitalizations and deaths worldwide, as well as stress from the fear of the disease and social uncertainties, from restriction measures and social isolation. Stress from social isolation impacts mental health, aggravating existing conditions and triggering neuropsychiatric symptoms in individuals with biopsychosocial vulnerability. During and immediately after the period of social restriction imposed by the pandemic, the scientific community carried out several research protocols. These revealed results that relevantly demonstrate the harmful effect of the stress induced by the pandemic situation. This narrative review reports and discusses research results demonstrating impairments in psychiatric disorders such as autism spectrum disorder, dementia, eating disorders, schizophrenia, anxiety, and depression. In this sense, the community has identified a significant negative influence of social isolation on the mental health of individuals through the modification of individual routines and the absence of social interactions. Moreover, the community identified perceived differences related to the impacts on men and women. In addition to studies showing the effect of social isolation on disorders, an evaluation of protocols with some possible therapeutic intervention strategies during times of social restriction was developed.

Stress and Kynurenine-Inflammation Pathway in Major Depressive Disorder.

Major depressive disorder (MDD) is one of the most prevalent disorders and causes severe damage to people's quality of life. Lifelong stress is one of the major villains in triggering MDD. Studies have shown that both stress and MDD, especially the more severe conditions of the disorder, are associated with inflammation and neuroinflammation and the relationship to an imbalance in tryptophan metabolism towards the kynurenine pathway (KP) through the enzymes indoleamine-2,3-dioxygenase (IDO), which is mainly stimulated by pro-inflammatory cytokines and tryptophan-2,3-dioxygenase (TDO) which is activated primarily by glucocorticoids. Considering that several pathophysiological mechanisms of MDD underlie or interact with biological processes from KP metabolites, this chapter addresses and discusses the function of these mechanisms. Activities triggered by stress and the hypothalamic-pituitary-adrenal (HPA) axis and immune and inflammatory processes, in addition to epigenetic phenomena and the gut-brain axis (GBA), are addressed. Finally, studies on the function and mechanisms of physical exercise in the KP metabolism and MDD are pointed out and discussed.

Quetiapine effect on depressive-like behaviors, oxidative balance, and inflammation in serum of rats submitted to chronic stress.

Major depressive disorder (MDD) etiology is still not completely understood, and many individuals resist the traditional treatments. Chronic exposure to stressful events can contribute to development and progression and be involved in biological changes underlying MDD. Among the biological mechanisms involved, inflammatory changes and oxidative balance are associated with MDD pathophysiology. Quetiapine, a second-generation antipsychotic, induces a better therapeutic response in individuals refractory to traditional treatments. The main objectives of this research were as follows: to evaluate the effect of chronic mild stress (CMS) on depressive-like behaviors, oxidative stress, and inflammation in adult rats; to evaluate the possible antidepressant, antioxidant, and anti-inflammatory effects of quetiapine. The animals were submitted to CMS protocols. At the end of the CMS, the animals were submitted to a chronic treatment for 14 days with the following drugs: quetiapine (20 mg/kg), imipramine (30 mg/kg), and escitalopram (10 mg/kg). At the end of the treatments, the animals were evaluated in the open field tests, anhedonia (splash test), and forced swimming. The animals were euthanized after the behavioral tests, and serum samples were collected. Myeloperoxidase (MPO) activity and interleukin-6 (IL-6) levels were analyzed. CMS induced an increase in depressive-like behaviors, and quetiapine significantly reduced these behaviors. MPO activity and IL-6 levels increased in the serum of animals submitted to CMS. Quetiapine significantly reduced MPO activity and IL-6 levels. These results corroborate other evidence, indicating that chronic stress is a relevant phenomenon in the etiology of depression and suggesting that quetiapine induces an antidepressant effect because it reduces oxidative and inflammatory mechanisms.

COVID-19, Oxidative Stress, and Neuroinflammation in the Depression Route.

COVID-19 is associated with oxidative stress, peripheral hyper inflammation, and neuroinflammation, especially in individuals with a more severe form of the disease. Some studies provide evidence on the onset or exacerbation of major depressive disorder (MDD), among other psychiatric disorders due to COVID-19. Oxidative stress and neuroinflammation are associated conditions, especially in the more severe form of MDD and in refractoriness to available therapeutic strategies. Inflammatory cytokines in the COVID-19 hyper inflammation process can activate the hypothalamic-pituitary-adrenal (HPA) axis and the indoleamine-2,3-dioxygenase (IDO) enzyme. IDO activation can reduce tryptophan and increase toxic metabolites of the kynurenine pathway, which increases glial activation, neuroinflammation, toxicity, and neuronal death. This review surveyed a number of studies and analyzed the mechanisms of oxidative stress, inflammation, and neuroinflammation involved in COVID-19 and depression. Finally, the importance of more protocols that can help elucidate the interaction between these mechanisms underlying COVID-19 and MDD and the possible therapeutic strategies involved in the interaction of these mechanisms are highlighted.

High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5'-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease. KEY MESSAGES: COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments.

Impact of COVID-19 in the Mental Health in Elderly: Psychological and Biological Updates.

Since December 2019, the world has been experiencing the challenge of facing coronavirus disease-19 (COVID-19), a severe infectious disease caused by the new coronavirus, SARS-CoV-2. The individuals with the most severe symptoms and the highest risk of death are the elderly and those with chronic illness. Among chronic conditions, those with a certain degree of chronic inflammation may predispose to a more severe evolution of COVID-19. Elderly with psychiatric disorders can present a persistent inflammatory state, a characteristic of the age's immunological senescence, but the disorder can accentuate that. Social isolation is still the safest way to avoid contamination. However, isolated older people may have or worsen mental health conditions due to isolation and health concerns. In this scenario, a SARS-CoV-2 infection may progress to more severe disease. Conversely, COVID-19 can predispose or aggravate psychiatric disorders, as it induces a cytokine storm, causing systemic hyper inflammation. It may damage the blood-brain barrier, resulting in inflammation in the central nervous system. Besides, SARS-CoV-2 is likely to reach and trigger an inflammatory process directly in the nervous system. This review makes an update about research on the mental health of the elderly during the pandemic. Also, it discusses the vulnerability of these individuals in the face of stress and in the case of contracting COVID-19, considering mainly the stress's hormonal and inflammatory mechanisms. Finally, the review points out possible care and attention strategies and entertainment and activities that can reduce the damage to mental and physical health and improve the elderly's quality of life. Graphical abstract Isolation and concerns about COVID-19 may harm elderly mental health. Immunosenescence and pandemic stress increase the risk of psychiatric disorders. Stress and disorders may potentiate the elderly's inflammation and COVID-19 symptoms. SARS-CoV-2 hyperinflammation is a risk factor for elderly psychiatric disorders.

Educação Popular e Saúde: O cuidado em saúde com o uso de plantas medicinais na cultura indígena kaigang / Popular Education and Health: Health care with the use of medicinal plants in kaigang indigenous culture

Este livro se propõe a resgatar a sabedoria do povo indígena Kaingang na essência de suas práticas, pelo conhecimento de uma complexidade tão instigante, como são "as plantas que curam". Nossa proposta é contribuir para o fortalecimento desse conhecimento ainda presente junto às comunidades indígenas, apresentando um diálogo entre saber popular e científico, numa abordagem genuína sobre o uso das plantas medicinais pelos povos indígenas da etnia Kaingang, acrescido de uma rica contextualização científica, mantendo, todavia, o cuidado de não se apropriar ou "tomar" para si o legado originário. Propõe-se também a construir pontes com saberes milenares, passados de geração em geração, que outorgam autonomia e resistência aos povos indígenas, os quais, por fatores sociais e políticos diversos, vêem cada dia mais sua existência ameaçada. Compreende-se que essa sabedoria transcende até mesmo o plano científico, ampliando para uma compreensão cosmológica, a qual, de forma sistêmica, integra saber popular, cultura, religiosidades, mitos e conhecimento, contribuindo, sobretudo, para a constituição de uma territorialidade, que ancestralmente produz uma cultura de resistência junto aos povos indígenas. Enseja-se assim, uma singela contribuição a uma cultura que insiste em re-existir, numa relação que pode tornar-se muito fecunda quando assume um diálogo emancipador, práxico e potencializador de ambos os saberes, com produção de novas sínteses.